chr4-7433320-G-A

Variant names:

• chr4-7433320-G-A
• rs757005290
• NM_001085382.2:c.1560C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001085382.2(PSAPL1):​c.1560C>T​(p.His520His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,405,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PSAPL1 NM_001085382.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 0 publications found

Genes affected

PSAPL1 (HGNC:33131): (prosaposin like 1) This gene encodes a protein that is related to the glycoprotein prosaposin. Based on sequence similarity between the encoded protein and prosaposin, it is predicted that the encoded protein is a preproprotein that is proteolytically processed to generate multiple protein products. These predicted products include saposins A-like, B-like, C-like, and D-like, which may play a role in the lysosomal degradation of sphingolipids. [provided by RefSeq, Jul 2015]

SORCS2 (HGNC:16698): (sortilin related VPS10 domain containing receptor 2) This gene encodes one family member of vacuolar protein sorting 10 (VPS10) domain-containing receptor proteins. The VPS10 domain name comes from the yeast carboxypeptidase Y sorting receptor Vps10 protein. Members of this gene family are large with many exons but the CDS lengths are usually less than 3700 nt. Very large introns typically separate the exons encoding the VPS10 domain; the remaining exons are separated by much smaller-sized introns. These genes are strongly expressed in the central nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSAPL1	NM_001085382.2	c.1560C>T	p.His520His	synonymous_variant	Exon 1 of 1	ENST00000319098.7	NP_001078851.1
SORCS2	NM_020777.3	c.548+36965G>A		intron_variant	Intron 2 of 26	ENST00000507866.6	NP_065828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSAPL1	ENST00000319098.7	c.1560C>T	p.His520His	synonymous_variant	Exon 1 of 1	6	NM_001085382.2	ENSP00000317445.4
SORCS2	ENST00000507866.6	c.548+36965G>A		intron_variant	Intron 2 of 26	1	NM_020777.3	ENSP00000422185.2
SORCS2	ENST00000511199.1	n.163+36965G>A		intron_variant	Intron 2 of 5	4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152220 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000306 AC: 2 AN: 65430 AF XY: 0.0000626

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000343

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000223 AC: 28 AN: 1253312 Hom.: 0 Cov.: 53 AF XY: 0.0000332 AC XY: 20 AN XY: 602804

African (AFR) AF: 0.0000732 AC: 2 AN: 27304

American (AMR) AF: 0.00 AC: 0 AN: 15016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18028

East Asian (EAS) AF: 0.0000309 AC: 1 AN: 32352

South Asian (SAS) AF: 0.000214 AC: 11 AN: 51366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5096

European-Non Finnish (NFE) AF: 0.0000129 AC: 13 AN: 1008698

Other (OTH) AF: 0.0000194 AC: 1 AN: 51654

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152220 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.59
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757005290; hg19: chr4-7435047;